BACKGROUND: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. PARTICIPANTS AND METHODS: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. RESULTS: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G-->A, 1100delC). CONCLUSION: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.
BACKGROUND: Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. PARTICIPANTS AND METHODS: We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. RESULTS: The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G-->A, 1100delC). CONCLUSION: A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations.
Authors: D W Bell; J M Varley; T E Szydlo; D H Kang; D C Wahrer; K E Shannon; M Lubratovich; S J Verselis; K J Isselbacher; J F Fraumeni; J M Birch; F P Li; J E Garber; D A Haber Journal: Science Date: 1999-12-24 Impact factor: 47.728
Authors: P Vahteristo; A Tamminen; P Karvinen; H Eerola; C Eklund; L A Aaltonen; C Blomqvist; K Aittomäki; H Nevanlinna Journal: Cancer Res Date: 2001-08-01 Impact factor: 12.701
Authors: Hanne Meijers-Heijboer; Ans van den Ouweland; Jan Klijn; Marijke Wasielewski; Anja de Snoo; Rogier Oldenburg; Antoinette Hollestelle; Mark Houben; Ellen Crepin; Monique van Veghel-Plandsoen; Fons Elstrodt; Cornelia van Duijn; Carina Bartels; Carel Meijers; Mieke Schutte; Lesley McGuffog; Deborah Thompson; Douglas Easton; Nayanta Sodha; Sheila Seal; Rita Barfoot; Jon Mangion; Jenny Chang-Claude; Diana Eccles; Rosalind Eeles; D Gareth Evans; Richard Houlston; Victoria Murday; Steven Narod; Tamara Peretz; Julian Peto; Catherine Phelan; Hong Xiang Zhang; Csilla Szabo; Peter Devilee; David Goldgar; P Andrew Futreal; Katherine L Nathanson; Barbara Weber; Nazneen Rahman; Michael R Stratton Journal: Nat Genet Date: 2002-04-22 Impact factor: 38.330
Authors: Mieke Schutte; Sheila Seal; Rita Barfoot; Hanne Meijers-Heijboer; Marijke Wasielewski; D Gareth Evans; Diana Eccles; Carel Meijers; Frans Lohman; Jan Klijn; Ans van den Ouweland; P Andrew Futreal; Katherine L Nathanson; Barbara L Weber; Douglas F Easton; Michael R Stratton; Nazneen Rahman Journal: Am J Hum Genet Date: 2003-02-27 Impact factor: 11.025
Authors: Xiangyang Dong; Liang Wang; Ken Taniguchi; Xianshu Wang; Julie M Cunningham; Shannon K McDonnell; Chiping Qian; Angela F Marks; Susan L Slager; Brett J Peterson; David I Smith; John C Cheville; Michael L Blute; Steve J Jacobsen; Daniel J Schaid; Donald J Tindall; Stephen N Thibodeau; Wanguo Liu Journal: Am J Hum Genet Date: 2003-01-17 Impact factor: 11.025
Authors: Hanne Meijers-Heijboer; Juul Wijnen; Hans Vasen; Marijke Wasielewski; Anja Wagner; Antoinette Hollestelle; Fons Elstrodt; Renate van den Bos; Anja de Snoo; Grace Tjon A Fat; Cecile Brekelmans; Shantie Jagmohan; Patrick Franken; Paul Verkuijlen; Ans van den Ouweland; Pamela Chapman; Carli Tops; Gabriela Möslein; John Burn; Henry Lynch; Jan Klijn; Riccardo Fodde; Mieke Schutte Journal: Am J Hum Genet Date: 2003-04-10 Impact factor: 11.025
Authors: E H Seppälä; T Ikonen; N Mononen; V Autio; A Rökman; M P Matikainen; T L J Tammela; J Schleutker Journal: Br J Cancer Date: 2003-11-17 Impact factor: 7.640
Authors: Hanna Janiszewska; Aneta Bak; Maria Pilarska; Marta Heise; Anna Junkiert-Czarnecka; Małgorzata Kuliszkiewicz-Janus; Małgorzata Całbecka; Bozena Jaźwiec; Dariusz Wołowiec; Kazimierz Kuliczkowski; Olga Haus Journal: Haematologica Date: 2011-11-04 Impact factor: 9.941
Authors: G Adler; M Parczewski; E Czerska; B Loniewska; M Kaczmarczyk; J Gumprecht; W Grzeszczak; A Szybinska; M Mossakowska; A Ciechanowicz Journal: J Appl Genet Date: 2010 Impact factor: 3.240
Authors: David C Kochan; Erin Winkler; Noralane Lindor; Gabriel Q Shaibi; Janet Olson; Pedro J Caraballo; Robert Freimuth; Joel E Pacyna; Carmen Radecki Breitkopf; Richard R Sharp; Iftikhar J Kullo Journal: NPJ Genom Med Date: 2020-05-04 Impact factor: 8.617
Authors: Urszula Teodorczyk; Cezary Cybulski; Dominika Wokołorczyk; Anna Jakubowska; Teresa Starzyńska; Małgorzata Lawniczak; Paweł Domagała; Katarzyna Ferenc; Krzysztof Marlicz; Zbigniew Banaszkiewicz; Rafał Wiśniowski; Steven A Narod; Jan Lubiński Journal: Fam Cancer Date: 2013-09 Impact factor: 2.375
Authors: Bo Johanneson; Shannon K McDonnell; Danielle M Karyadi; Scott J Hebbring; Liang Wang; Kerry Deutsch; Laura McIntosh; Erika M Kwon; Miia Suuriniemi; Janet L Stanford; Daniel J Schaid; Elaine A Ostrander; Stephen N Thibodeau Journal: Hum Genet Date: 2007-12-08 Impact factor: 4.132